Among hydroxybenzoic acids and their esters, p-hydroxybenzoic acids and their esters are often used as food and drug preservatives. Gallic acid esters can inhibit the synthesis of thromboxane A2 (TXA2). It has a stronger and faster effect against platelets aggregation than aspirin and has been used in solution for injection. Gallic acid has been proven to inhibit hepatitis B virus replication (see Journals of Guangzhou Liberation Army High Specialized School, 1998, 26 (2):5-7).
Chinese Patent No. 1411339A and U.S. Pat. No. 6,294,186 disclosed an antimicrobial composition. The composition includes a safe and effective amount of benzoic acid analogues, which have the following structure (II):

Wherein, R1, R2, R4 and R5 were independently H, OH, F, I, Br, Cl, SH, NH2, CN, alkyl, alkoxy, NR2, OR, NO2, COR, CONR2, CO2R or SO3R, wherein R was independently H, alkyl or alkoxy; R3 was independently H, OH, F, I, Br, Cl, SH, CN, alkyl, alkoxy, OR, NO2, COR, CONR2, CO2R or SO3R, wherein R was independently H, alkyl or alkoxy. The aforesaid patent references also pointed out the most preferred embodiment as salicylic acid (“2-hydroxybenzoic acid”), benzoic acid or their combination; they also limited the pH range in which these compounds could be used to 1-7.
Although viruses are the smallest known pathogenic microorganisms, they spread most widely. Today, almost three quarters of contagious diseases in the world are caused by viruses. In clinical diagnosis, many diseases are related to virus infection.
Papillomavirus is a DNA virus that infects the skin or mucosal surfaces of humans or animals. Condyloma acuminata, also called genital warts or venereal warts, is a benign skin mucosa growth induced by human papillomavirus (HPV). It is one of the most frequently seen sexually transmitted diseases and is closely related to inflammation and cancer of the genital organs. Currently, podophyllotoxin is one of the drugs for treating genital warts. Its advantage is short treatment time and disadvantage is skin irritation and severe side effects, including pain, edema, erosion and so on. Recombinant interferon α-2β gel is recognized as an effective external drug to treat genital warts.
Recent researches indicated that 29.3% of the patients of cervical erosion were tested HPV positive while the positive rate among the normal population is only 11.1% (Fuqiang Chen, Tumor Prevention Magazine, 2001, 8 (4): 342-344; Chenkang Xu, Journal of Zhongshan Medical University, 1998, 19 (3): 223-226). It was reported that the high-risk HPV16, HPV18 were expressed in about 69% of chronic cervicitis patients and that these subtypes were detected at an increasing rate as the degree of the cervical erosion increased (Ahn ws et al, J. Cell Biochem. Suppl., 1997; 28-29: 133-139). The difference of the detection rates of HPV16 and HPV18 between granular or papillary erosion and normal cervix was significant. The positive rate of HPV16 and HPV18 in cervix cancer could be as high as 83.33% when detected by PCR. The DNA of high risk HPV could integrate into the chromosomes of the host cells and then produce E6 and E7 tumor proteins. E6 and E7 could respectively inhibit anti-cancer genes p53 and Rb. As a result, cells would lose the control of p53 and Rb. This would cause cells in the steady state to grow actively and might become cancerous. If HPV16 remains in the cells, it could turn the cervix pathological changes into cancer. Different from the pudendum infection, cervix HPV infection mainly involves HPV 16/18 and usually will not cause warts. It can exist as latent infection for a long time and induce atypical hyperplasia at first and become cancerous when the other factors add on.
Herpes viruses are a virus family with many virus subtypes. Herpes simplex virus (HSV) is one of the most common subtypes of herpes viruses. HSV is a double stranded DNA virus and can enter into target organisms through mouth, respiratory passage, genital tract mucosa, broken skin and many other channels. HSV are further divided into two sub-subtypes, HSV-1 and HSV-2. It is a quite common infection among humans and the infection rate is as high as 80˜90%. Typical symptoms include clusters of blisters on certain parts of the mucosa and skin, while occasionally serious systemic disease may occur and do harm to the internal organs. Previous researches indicated that HSV-1 and HSV-2 might separately be related to lip cancer, vulva cancer and cervix cancer and lots of attentions have been drawn to them (Sun He et al., China Practical Gynaecology and Obstetrics Journal, 2001, 17 (7):407-409). Presently, drugs for treating HSV infection include idoxuridine, cytosine arabinoside, vidarabine, bromovinyl uridine, acyclovir and so on. But the treatment time of these drugs are quite long, about 5-7 days.
Varicella zoster virus (VZV), also called herpes zoster, is another commonly found herpes virus. VZV is closely related to HSV and shares much genome homology. Initial VZV infection may cause chicken pox, which in a few rare cases, may result in encephalitis or pneumonia. After the initial infection, VZV could remain in the host's nervous system in a latent state. In about 10-20% of cases, VZV reactivates later in the life of the host to cause shingles and related complications.
Antiviral drugs useful for treating hepatitis B virus (HBV) infection, such as vidarabine, vidarabine phosphate, acyclovir and zidovudine, which were tested in the 1980s, were not used to treat hepatitis B anymore due to severe side effects and high toxicity. Recently, many nucleoside drugs, such as Lamivudine, famciclovir, lobucavir, adefovir, FTC, FMAU, FDDC, BMS 200475 and so on, were developed and they had significant inhibiting effect on HBV. Unfortunately, viruses may mutate and become drug resistant after long term use of these drugs. Furthermore, these drugs need to be taken for a long time because short term use only has temporary effect.
There is a continuing need for new drugs useful for the prevention and/or treatment of virus infection such as HBV, papillomavirus and herpes virus infection.